2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF2 α compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,740, filed Feb. 13, 1976, now pending issuance as a U.S. Patent.

The present invention relates to prostaglandin analogs, for which the essential material constituting disclosure therefor is incorporated by reference here from Ser. No. 820,974, filed Aug. 1, 1977, which is a divisional application of Ser. No. 657,740. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is ##STR2## wherein Z₄ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, wherein g is one, 2, or 3;Wherein R₇ is ##STR3## WHEREIN Z₃ is oxa or methylene, s is zero, one, 2, or 3, and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl; Wherein L₁ is ##STR4## or a mixture of ##STR5## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different with the proviso that one of R₃ and R₄ is methyl only when the other is hydrogen or methyl, with the further proviso that one or both of R₃ and R₄ is fluoro only when Z₃ is methylene; Wherein M₁ is ##STR6## wherein R₅ and R₆ are hydrogen or methyl, with the proviso that one of R₅ and R₆ is methyl only when the other is hydrogen; and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein D is ##STR7##
 3. A compound according to claim 2, wherein M₁ is ##STR8##
 4. A compound according to claim 3, wherein g is one.
 5. A compound according to claim 4, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 6. 15-epi-2,2-difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 4. 7. A compound according to claim 2, wherein M₁ is ##STR9##
 8. A compound according to claim 7, wherein g is three.
 9. A compound according to claim 7, wherein g is one.
 10. A compound according to claim 9, wherein R₃ and R₄ are both hydrogen.
 11. A compound according to claim 10, wherein R₅ is methyl.
 12. 2,2-Difluoro-15-methyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 11. 13. 2,2-Difluoro-15-methyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 11. 14. A compound according to claim 10, wherein R₆ is methyl.
 15. 2,2-Difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, 15-methyl ether, a compound according to claim
 14. 16. 2,2-Difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, 15-methyl ether, a compound according to claim
 14. 17. A compound according to claim 10, wherein R₅ and R₆ are both hydrogen.
 18. 2,2-Difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 17. 19. 2,2-Difluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 17. 20. A compound according to claim 9, wherein at least one of R₃ and R₄ is methyl.
 21. A compound according to claim 20, wherein R₃ and R₄ are both methyl.
 22. A compound according to claim 21, wherein R₅ is methyl.
 23. 2,2-Difluoro-15,16,16-trimethyl-13,14-didehydro-8β,12.alpha.-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 22. 24. A compound according to claim 21, wherein R₆ is methyl.
 25. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12.alpha.-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, 15-methyl ester, a compound according to claim
 24. 26. A compound according to claim 21, wherein R₅ and R₆ are both hydrogen.
 27. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 26. 28. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 26. 29. A compound according to claim 9, wherein at least one of R₃ and R₄ is fluoro.
 30. A compound according to claim 29, wherein R₃ and R₄ are both fluoro.
 31. A compound according to claim 30, wherein R₅ is methyl.
 32. 2,2,16,16-Tetrafluoro-15-methyl-13,14-didehydro-8β,12.alpha.-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 31. 33. A compound according to claim 30, wherein R₆ is methyl.
 34. 2,2,16,16-Tetrafluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, 15-methyl ether, a compound according to claim
 33. 35. A compound according to claim 30, wherein R₅ and R₆ are both hydrogen.
 36. 2,2,16,16-Tetrafluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 35. 37. 2,2,16,16-Tetrafluoro-13,14-didehydro-8β,12α-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 35. 38. A compound according to claim 1, wherein D is ##STR10##
 39. A compound according to claim 38, wherein M₁ is ##STR11##
 40. A compound according to claim 39, wherein g is one.
 41. A compound according to claim 40, wherein R₃, R₄, R₅, and R₆ are all hydrogen.
 42. 15-epi-2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 41. 43. A compound according to claim 38, wherein M₁ is ##STR12##
 44. A compound according to claim 43, wherein g is three.
 45. A compound according to claim 43, wherein g is one.
 46. A compound according to claim 45, wherein R₃ and R₄ are both hydrogen.
 47. A compound according to claim 46, wherein R₅ is methyl.
 48. 2,2-Difluoro-15-methyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 47. 49. 2,2-Difluoro-15-methyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 47. 50. A compound according to claim 46, wherein R₆ is methyl.
 51. 2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, 15-methyl ether, a compound according to claim
 50. 52. 2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF.sub.2 α, methyl ester, 15-methyl ether, a compound according to claim
 50. 53. A compound according to claim 46, wherein R₅ and R₆ are both hydrogen.
 54. 2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 50. 55. 2,2-Difluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 53. 56. A compound according to claim 45, wherein at least one of R₃ and R₄ is methyl.
 57. A compound according to claim 56, wherein R₃ and R₄ are both methyl.
 58. A compound according to claim 57, wherein R₅ is methyl.
 59. 2,2-Difluoro-15,16,16-trimethyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 58. 60. A compound according to claim 57, wherein R₆ is methyl.
 61. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, 15-methyl ether, a compound according to claim
 60. 62. A compound according to claim 57, wherein R₅ and R₆ are both hydrogen.
 63. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, a compound according to claim
 62. 64. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 62. 65. A compound according to claim 45, wherein at least one of R₃ and R₄ is fluoro.
 66. A compound according to claim 65, wherein R₃ and R₄ are both fluoro.
 67. A compound according to claim 66, wherein R₅ is methyl.
 68. 2,2,16,16-Tetrafluoro-15-methyl-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 67. 69. A compound according to claim 66, wherein R₆ is methyl.
 70. 2,2,16,16-Tetrafluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, 15-methyl ether, a compound according to claim
 69. 71. A compound according to claim 66, wherein R₅ and R₆ are both hydrogen.
 72. 2,2,16,16-Tetrafluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF.sub.2 α, a compound according to claim
 71. 73. 2,2,16,16-Tetrafluoro-13,14-didehydro-11-deoxy-17-phenyl-18,19,20-trinor-PGF₂ α, methyl ester, a compound according to claim
 71. 